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. 1995 Oct;72(4):968–972. doi: 10.1038/bjc.1995.443

Metallothionein expression in human breast cancer.

H Goulding 1, B Jasani 1, H Pereira 1, A Reid 1, M Galea 1, J A Bell 1, C W Elston 1, J F Robertson 1, R W Blamey 1, R A Nicholson 1, et al.
PMCID: PMC2034037  PMID: 7547250

Abstract

Metallothioneins are ubiquitous low molecular weight proteins characterised by high cysteine content and affinity for binding heavy metals. Abnormal metallothionein function and expression have been implicated in various disease states, including neoplasia. The aim of this study was to investigate metallothionein expression in human breast carcinoma. Sections of routinely fixed and processed blocks of tumour from 100 consecutive cases of primary operable breast carcinoma were stained for metallothionein using a recently developed monoclonal antibody and a standard immunohistochemical technique. Expression was scored on the basis of microscopical assessment of percentage of tumour cells staining. One patient was lost to follow-up and excluded from the study. A significant association (P < 0.0001) was observed between metallothionein expression and tumour type, with low levels being observed in tumours of good prognostic type. There was also a significant association with local recurrence (P < 0.02) and a significant difference (P < 0.02) in both survival and disease-free interval between tumours showing low and high levels of expression, the latter indicating a poor prognosis. No relationship was observed with patient age, tumour size, lymph node stage, histological grade, vascular invasion, menopausal status or oestrogen receptor status. The assessment of metallothionein expression in human breast cancer appears to provide prognostic information and may have important implications for understanding its development.

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Selected References

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  1. Andrews P. A., Murphy M. P., Howell S. B. Metallothionein-mediated cisplatin resistance in human ovarian carcinoma cells. Cancer Chemother Pharmacol. 1987;19(2):149–154. doi: 10.1007/BF00254568. [DOI] [PubMed] [Google Scholar]
  2. Angel P., Pöting A., Mallick U., Rahmsdorf H. J., Schorpp M., Herrlich P. Induction of metallothionein and other mRNA species by carcinogens and tumor promoters in primary human skin fibroblasts. Mol Cell Biol. 1986 May;6(5):1760–1766. doi: 10.1128/mcb.6.5.1760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bier B., Douglas-Jones A., Tötsch M., Dockhorn-Dworniczak B., Böcker W., Jasani B., Schmid K. W. Immunohistochemical demonstration of metallothionein in normal human breast tissue and benign and malignant breast lesions. Breast Cancer Res Treat. 1994;30(3):213–221. doi: 10.1007/BF00665963. [DOI] [PubMed] [Google Scholar]
  4. Compere S. J., Palmiter R. D. DNA methylation controls the inducibility of the mouse metallothionein-I gene lymphoid cells. Cell. 1981 Jul;25(1):233–240. doi: 10.1016/0092-8674(81)90248-8. [DOI] [PubMed] [Google Scholar]
  5. Ellis I. O., Galea M., Broughton N., Locker A., Blamey R. W., Elston C. W. Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology. 1992 Jun;20(6):479–489. doi: 10.1111/j.1365-2559.1992.tb01032.x. [DOI] [PubMed] [Google Scholar]
  6. Elston C. W., Ellis I. O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403–410. doi: 10.1111/j.1365-2559.1991.tb00229.x. [DOI] [PubMed] [Google Scholar]
  7. Fresno M., Wu W., Rodriguez J. M., Nadji M. Localization of metallothionein in breast carcinomas. An immunohistochemical study. Virchows Arch A Pathol Anat Histopathol. 1993;423(3):215–219. doi: 10.1007/BF01614773. [DOI] [PubMed] [Google Scholar]
  8. Hamer D. H. Metallothionein. Annu Rev Biochem. 1986;55:913–951. doi: 10.1146/annurev.bi.55.070186.004405. [DOI] [PubMed] [Google Scholar]
  9. Jasani B., Elmes M. E. Immunohistochemical detection of metallothionein. Methods Enzymol. 1991;205:95–107. doi: 10.1016/0076-6879(91)05091-9. [DOI] [PubMed] [Google Scholar]
  10. KAGI J. H., VALEE B. L. Metallothionein: a cadmium- and zinc-containing protein from equine renal cortex. J Biol Chem. 1960 Dec;235:3460–3465. [PubMed] [Google Scholar]
  11. Kaina B., Lohrer H., Karin M., Herrlich P. Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2710–2714. doi: 10.1073/pnas.87.7.2710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kelley S. L., Basu A., Teicher B. A., Hacker M. P., Hamer D. H., Lazo J. S. Overexpression of metallothionein confers resistance to anticancer drugs. Science. 1988 Sep 30;241(4874):1813–1815. doi: 10.1126/science.3175622. [DOI] [PubMed] [Google Scholar]
  13. Murphy D., McGown A. T., Crowther D., Mander A., Fox B. W. Metallothionein levels in ovarian tumours before and after chemotherapy. Br J Cancer. 1991 May;63(5):711–714. doi: 10.1038/bjc.1991.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nicholson R. I., Campbell F. C., Blamey R. W., Elston C. W., George D., Griffiths K. Steroid receptors in early breast cancer: value in prognosis. J Steroid Biochem. 1981 Dec;15:193–199. doi: 10.1016/0022-4731(81)90275-2. [DOI] [PubMed] [Google Scholar]
  15. Pinder S. E., Ellis I. O., Galea M., O'Rouke S., Blamey R. W., Elston C. W. Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology. 1994 Jan;24(1):41–47. doi: 10.1111/j.1365-2559.1994.tb01269.x. [DOI] [PubMed] [Google Scholar]
  16. Renan M. J., Dowman P. I. Increased radioresistance of tumor cells exposed to metallothionein-inducing agents. Radiat Res. 1989 Dec;120(3):442–455. [PubMed] [Google Scholar]
  17. Schilder R. J., Hall L., Monks A., Handel L. M., Fornace A. J., Jr, Ozols R. F., Fojo A. T., Hamilton T. C. Metallothionein gene expression and resistance to cisplatin in human ovarian cancer. Int J Cancer. 1990 Mar 15;45(3):416–422. doi: 10.1002/ijc.2910450306. [DOI] [PubMed] [Google Scholar]
  18. Schmid K. W., Ellis I. O., Gee J. M., Darke B. M., Lees W. E., Kay J., Cryer A., Stark J. M., Hittmair A., Ofner D. Presence and possible significance of immunocytochemically demonstrable metallothionein over-expression in primary invasive ductal carcinoma of the breast. Virchows Arch A Pathol Anat Histopathol. 1993;422(2):153–159. doi: 10.1007/BF01607167. [DOI] [PubMed] [Google Scholar]
  19. Thornalley P. J., Vasák M. Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. Biochim Biophys Acta. 1985 Jan 21;827(1):36–44. doi: 10.1016/0167-4838(85)90098-6. [DOI] [PubMed] [Google Scholar]
  20. Webb M., Cain K. Functions of metallothionein. Biochem Pharmacol. 1982 Jan 15;31(2):137–142. doi: 10.1016/0006-2952(82)90202-7. [DOI] [PubMed] [Google Scholar]
  21. Webber M. M., Rehman S. M., James G. T. Metallothionein induction and deinduction in human prostatic carcinoma cells: relationship with resistance and sensitivity to adriamycin. Cancer Res. 1988 Aug 15;48(16):4503–4508. [PubMed] [Google Scholar]

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